The invention relates to tetrahydro-1,3-oxazin-2-ones. More particularly the invention concerns a new process for the formation of this known class of compounds.
Tetrahydro-1,3-oxazin-2-ones are known compounds that demonstrate utility as drugs for stimulation of the central nervous system and as barbituate antagonists, as disclosed by E. Testa et al. in Farmaco (Pavia) Ed. Sci., 13, 437 (1958) (CA 53:6099) and by Krewel Lueffer G.m.b.h., French patent M 1626 (CA 58:12576) which teaching is incorporated herein by reference. The compounds are also useful intermediates in the preparation of additional pharmaceuticals having psychotropic utility.
In the past, several methods have been disclosed for the preparation of tetrahydro-1,3-oxazin-2-ones and substituted derivatives thereof. Suitable methods have involved the reaction of 1,3-propanolamine with a reactive carbonyl-containing compounds such as phosgene (USP 2,940,971), ethylchloroformate (Berichte, 65B, 385 (1932)), or diethyl carbonate (French patent M 1626, CA 58:12576).
In addition, tetrahydro-1,3-oxazin-2-ones have been prepared by the reaction of 1,3-halopropanols with potassium cyanate in a polar solvent such as N,N-dimethylformamide (Japanese Kokai 11,837 (1960)).
It is also known to prepare N-phenyl-substituted tetrahydro-1,3-oxazin-2-ones by the reaction of phenyl isocyanate with a 1,3-dioxan-2-one in the presence of a catalytic amount of lithium chloride catalyst.